Medetomidine is a racemic mixture of two optical enantiomers, which namely levmedetomidine (LEV) and dexmedetomidine (DEX), at an equal ratio (MacDonald et al., 1991; Savola and Virtanen, 1991). Such compound has high selectivity on 2-epinephrine acceptor, and is a novel alpha2-receptor stimulant with 4-replaced imidazole ring (Savola et al, 1986).
At present, there are several known methods for preparing the medetomidine.
Kudzma et al. put forward a multi-step method for preparing the medetomidine. This method has disadvantages of using compounds with high flammability and high corrosion, such as butyl lithium, and of reacting at a low temperature of about −78° C.
The European patent EP1918282 discloses a preparation method of medetomidine and its salt. According to the method, the transmetalation of the halogenated imidazole is carried out by using the Grignard reagent, and then imidazole reacts with 2,3-dimethylbezaldehyde to generate alcohol, and the alcohol is oxidized by using manganese dioxide to generate 2,3-dimethyl phenyl-1-trityl-imidazole-4-ketone. The method is disadvantaged in using trityl chloride to perform nitrogen protection and deprotection on imidazole, so the operation process is complicated.
Cordi et al. disclose a preparation method of medetomidine in tartrate form. This method has the disadvantage that the raw material is very expensive.
GB 2453982 discloses a preparation method of medetomidine, including reaction between 2,3-dimethyl-methylbenzyl alcohol and N-trimethylsilylimidazole. The method is disadvantaged in using strong Lewis acid and excessive reagents.